Phage-plasmids spread antibiotic resistant genes.
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB52357 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| CALYCH02.master.dat | Other | |||
| CALYCI02.master.dat | Other | |||
| CALYCJ02.master.dat | Other | |||
| CALYCK02.master.dat | Other |
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Project description:hvKP ATCC43816 and its lytic phage H5 were employed as a phage-antibiotic combination model. Based on the comprehensive characterization of phages, including cryo-electron microscopy, we evaluated the synergic effect of H5 on bacterial killing in vitro when combined with multiple antibiotics, and analyzed the advantages of phage-antibiotic combinations from an evolutionary perspective and proposes a novel PAS mechanism by using ceftazidime as an example.
2023-09-14 | GSE237490 | GEO
Project description:Antibiotic resistance is exacerbated by the exchange of antibiotic resistance genes (ARGs) between microbes from diverse habitats. Plasmids are important ARGs mobile elements and are spread by horizontal gene transfer (HGT). In this study, we demonstrated the presence of multi-resistant plasmids from inhalable particulate matter (PM) and its effect on gene horizontal transfer. Three transferable multi-resistant plasmids were identified from PM in a hospital, using conjugative mating assays and nanopore sequencing. pTAir-3 contained 26 horizontal transfer elements and 10 ARGs. Importantly pTAir-5 harbored carbapenem resistance gene (blaOXA) which shows homology to plasmids from human and pig commensal bacteria, thus indicating that PM is a media for antibiotic resistant plasmid spread. In addition, 125 μg/mL PM2.5 and PM10 significantly increased the conjugative transfer rate by 110% and 30%, respectively, and augmented reactive oxygen species (ROS) levels. Underlying mechanisms were revealed by identifying the upregulated expressional levels of genes related to ROS, SOS, cell membranes, pilus generation, and transposition via genome-wide RNA sequencing. The study highlights the airborne spread of multi-resistant plasmids and the impact of inhalable PM on the horizontal transfer of antibiotic resistance.
2022-10-31 | GSE159850 | GEO
Project description:Antibiotic resistance is rapidly spreading via the horizontal transfer of resistance genes in mobile genetic elements. While plasmids are key drivers of this process, few integrative phages encode antibiotic resistance genes. Here, we find that phage-plasmids, elements that are both phages and plasmids, often carry antibiotic resistance genes. We found 60 phage-plasmids with 184 antibiotic resistance genes, providing resistance for broad-spectrum-cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and colistin. These genes are in a few hot spots, seem to have been cotranslocated with transposable elements, and are often in class I integrons, which had not been previously found in phages. We tried to induce six phage-plasmids with resistance genes (including four with resistance integrons) and succeeded in five cases. Other phage-plasmids and integrative prophages were coinduced in these experiments. As a proof of concept, we focused on a P1-like element encoding an extended spectrum β-lactamase, blaCTX-M-55. After induction, we confirmed that it is capable of infecting and converting four other E. coli strains. Its reinduction led to the further conversion of a sensitive strain, confirming that it is a fully functional phage. This study shows that phage-plasmids carry a large diversity of clinically relevant antibiotic resistance genes that they can transfer across bacteria. As plasmids, these elements seem plastic and capable of acquiring genes from other plasmids. As phages, they may provide novel paths of transfer for resistance genes because they can infect bacteria that are distant in time and space from the original host. As a matter of alarm, they may also mediate transfer to other types of phages. IMPORTANCE The dissemination of antimicrobial resistance is a major threat to global health. Here, we show that a group of temperate bacterial viruses (phages), termed phage-plasmids, commonly encode different and multiple types of resistance genes of high clinical importance, often in integrons. This is unexpected, as phages typically do not carry resistance genes and, hence, do not confer upon their hosts resistance via infection and genome integration. Our experiments with phage-plasmids isolated from clinical settings confirmed that they infect sensitive strains and render them antibiotic resistant. The spread of antibiotic resistance genes by phage-plasmids is worrisome because it dispenses cell-to-cell contact, which is necessary for canonical plasmid transfer (conjugation). Furthermore, their integrons become genetic platforms for the acquisition of novel resistance genes.
| S-EPMC9600943 | biostudies-literature
Project description:The emergence of carbapenem-resistant Acinetobacter baumannii has been increasingly reported, leading to more challenges in treating its infections. With the development of phage therapy and phage-antibiotic combinations, it is possible to improve the treatment of bacterial infections. In the present study, a vB_AbaP_WU2001 (vWU2001 for short) phage-specific CRAB was isolated and the genome size is 40,792 bp in length. The novel phage vWU2001 belongs to the Autographiviridae family and the order Caudovirales. Shotgun proteomics identified 289 proteins. The broad host range phage vWU2001 displayed a high adsorption rate, short latent period, large burst size and good stability. The phage could reduce preformed biofilms and inhibit biofilm formation. The combination of phage vWU2001 and colistin had significantly higher bacterial growth inhibition activity than that of phage, or colistin alone. The efficacy of the combined treatment was also evaluated in Galleria mellonella. The evaluation of its therapeutic potential revealed that the combination of phage and colistin showed a significantly greater increase in G. mellonella survival and clearance of bacterial number compared to that of phage or colistin alone, indicating that the combination was synergistic against CRAB. The results demonstrated that phage vWU2001 has the potential to be developed as an antibacterial agent.
2021-09-04 | PXD028206 | JPOST Repository
Project description:Cationic antimicrobial peptides (CAPs) are promising novel alternatives to conventional antibacterial agents, but the overlap in resistance mechanisms between small-molecule antibiotics and CAPs is unknown. Does evolution of antibiotic resistance decrease (cross-resistance) or increase (collateral sensitivity) susceptibility to CAPs? We systematically addressed this issue by studying the susceptibilities of a comprehensive set of antibiotic resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic resistant bacteria frequently showed collateral sensitivity to CAPs, while cross-resistance was relatively rare. We identified clinically relevant multidrug resistance mutations that simultaneously elevate susceptibility to certain CAPs. Transcriptome and chemogenomic analysis revealed that such mutations frequently alter the lipopolysaccharide composition of the outer cell membrane and thereby increase the killing efficiency of membrane-interacting antimicrobial peptides. Furthermore, we identified CAP-antibiotic combinations that rescue the activity of existing antibiotics and slow down the evolution of resistance to antibiotics. Our work provides a proof of principle for the development of peptide based antibiotic adjuvants that enhance antibiotic action and block evolution of resistance.
2018-03-29 | GSE96706 | GEO
Project description:Phage-Antibiotic Combinations Against Klebsiella pneumoniae
| PRJNA995503 | ENA
Project description:Bacteriophages are potent therapeutics against biohazardous bacteria that are rapidly acquiring multidrug resistance. However, routine administration of bacteriophage therapy is currently impeded by a lack of safe phage production methodologies and insufficient phage characterization. We thus developed a versatile cell-free platform for host-independent production of phages targeting gram-positive and gram-negative bacteria. A few microliters of a one-pot reaction produces effective doses of phages against potentially antibiotic-resistant bacteria such as enterohemorrhagic E. coli (EAEC) and Yersinia pestis, which also possibly pose threats as biological warfare agents. We also introduce a method for transient, non-genomic phage engineering to safely confer additional functions, such as a purification tag or bioluminescence for host detection, for only one replication cycle. Using high-resolution and time-resolved mass spectrometry, we validated the expression of 40 hypothetical proteins from two different phages (T7 and CLB-P3) and identified genes in the genome of phage T7 that express exceptionally late during phage replication. Our comprehensive methodology thus allows for accelerated reverse and forward phage engineering as well as for safe and customized production of clinical-grade therapeutic bacteriophages.
2022-07-20 | PXD019543 | Pride
Project description:Pseudomonas syringae pv. phaseolicola (Pph) is a significant bacterial pathogen of agricultural crops, and phage Φ6 and other members of the dsRNA virus family Cystoviridae undergo lytic (virulent) infection of Pph, using the type IV pilus as the initial site of cellular attachment. Despite the popularity of Pph/phage Φ6 as a model system in evolutionary biology, Pph resistance to phage Φ6 remains poorly characterized. To investigate differences between phage Φ6 resistant Pseudomonas syringae pathovar phaseolicola strains, we performed expression analysis of super and non piliated strains of Pseudomonas syringae to determine the genetic cause of resistance to viral infection.
2016-03-15 | E-MTAB-4053 | biostudies-arrayexpress
Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.
2024-10-01 | GSE272297 | GEO
Project description:Pathogen genomic surveillance as a scalable framework for precision phage therapy - phage resistant genomes
| PRJEB64574 | ENA